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Summary Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR‐T) with non‐negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19‐directed CAR‐T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post‐CAR‐T, we compiled a retrospective single‐centre cohort of non‐Hodgkin lymphoma patients. Only commercial CAR‐T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR‐T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67–5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post‐CAR‐T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co‐occurred with cytokine release syndrome and were associated with higher post‐CAR‐T infusion peak levels of IL‐10, TNF‐alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39–19.6]) and using CAR‐T product with a CD28‐costimulatory domain (OR = 5.17 [1.72–18.6]). Atrial arrhythmias following CD19‐CAR‐T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR‐T product with a CD28 costimulatory domain. [ABSTRACT FROM AUTHOR]

Background: Uric acid is an emerging biomarker for cardiovascular morbidity and mortality, but its association with all-cause mortality and ECG findings remains unestablished, specifically among older adults. We aimed to evaluate the association between serum uric acid (SUA) with incidental findings of ECG abnormalities and with long-term all-cause mortality. Methods: We conducted a prospective cohort study of 851 community dwelling men and women, who were examined between 1999 and 2008, and followed over 20 years until December 2019 for all-cause mortality. Subjects free of Gout or diuretics treatment at baseline were included. SUA was categorized according to sex-specific tertiles and evaluated against baseline ECG findings and all-cause mortality. Results: Mean baseline age was 72±7 years and 416 (49%) were females. Ischemic changes on ECG were observed in 85 (10.0%) participants, of them 36 (13.5%) belonged to the upper SUA tertile and 49 (8.4%) to the lower ones (p = 0.02). Multivariable logistic regression showed 80% higher odds for ischemic changes on ECG among participants in the high SUA tertile (adjusted-OR = 1.8, 95%CI 1.1–2.9, p = 0.03) compared with the lower SUA two-tertiles. During a median follow-up of 14 years, 380 (44.7%) participants died. SUA ≥5.3 mg/dl for women and ≥ 6.2 mg/dl for men, was associated with a 30% greater risk for all-cause mortality in a multivariable Cox regression model (HR = 1.3, 95%CI: 1.0–1.6, p = 0.03). Conclusions: High SUA level was associated with ischemic changes on ECG and with an increased risk for all-cause mortality over 20 years of follow-up among community dwelling older adults free of Gout. Even lower sex-specific thresholds of SUA were associated with all-cause mortality than previously proposed. SUA should be considered as a biomarker for cardiovascular risk and all-cause mortality. [ABSTRACT FROM AUTHOR]

Characterize ocular adverse events (oAEs) caused by immune checkpoint inhibitors (ICIs). Retrospective analysis of 41,674 cancer patients in the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database receiving anti-PD-1/PD-L1, anti-CTLA-4, or anti-PD-1+ anti-CTLA-4 combination. Reporting odds ratio (ROR) was used to approximate oAE rate across regimens and indications. The most common indications were lung cancer (27.3%) and melanoma (22.7%); 76.3% received anti-PD-1/PD-L1 monotherapy. 1,268 patients (3.0%) reported oAEs, namely vision disorders (30.8%), uveitis (15.1%), and retinal, lacrimal, and optic nerve disorders (10.7%, 9.0%, 8.4%). Melanoma showed the highest proportion of uveitis (117/9,471 cases; 1.2%). Addition of anti-CTLA-4 to anti-PD-1 increased the ROR of uveitis from 4.77 (95% CI 3.83–5.94) to 17.1 (95% CI 12.9–22.7). Among anti-PD-1/PD-L1 cases, uveitis was differentially reported in melanoma (ROR 14.7, 95% CI 10.7–20.2) compared with lung cancer (ROR 2.67, 95% CI 1.68–4.23). ICI-induced oAEs are rare, and uveitis is significantly associated with melanoma and anti-PD-1+ anti-CTLA-4 combination. [ABSTRACT FROM AUTHOR]

Aim: There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID‐19) pandemic. We analysed real‐world data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ‐associated cardiovascular adverse events (CVAEs) in pre‐COVID‐19 reports. Methods: We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014‐9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025). Results: The full database contained 6 677 225 reports with a mean (±SD) age of 53 (±17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3‐35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3‐6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8‐2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9‐2.7], all IC₀₂₅ > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ‐associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively). Conclusion: In a real‐world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ‐associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off‐label indication, especially for patients with cardiac disorders. [ABSTRACT FROM AUTHOR]

Purpose. To report a case of a 34-year-old male with recurrent herpes zoster ophthalmicus (HZO) preceded by a 6-week cycle of anabolic steroids and high-dose amino acid supplementation. Case Presentation. A 34-year-old man presented to our institution for left eye pain for one week associated with a vesicular rash in the V1 dermatome, respecting the midline. The patient had no significant past medical or past ocular history, including systemic immunosuppressive agents or HIV. However, prior to the onset of his symptoms the patient had completed a 6-week course of anabolic steroids including trenbolone, deca-durabolin, and testosterone as well as high-dose arginine supplementation averaging more than 40 grams a day. The best-corrected vision was 20/25 OS with slit-lamp examination remarkable for punctate staining and pseudodendrites at 6 o'clock, outside the visual axis. The patient was treated with oral acyclovir 800 mg five times a day for seven days along with prednisolone QID and moxifloxacin QID which was tapered over a month. Four months after resolution, the patient developed a recurrent HZO keratitis preceded by another cycle of anabolic steroids and amino acid supplementation. Conclusion. In vitro L-arginine supplementation has been associated with the proliferation and virulence of a variety of herpes viruses. Anabolic steroids have also been demonstrated by various studies to negatively affect cell-mediated immunity necessary to prevent viral infection. Thus, it is possible that anabolic steroids in conjunction with increased L-arginine intake may have precipitated a recurrent HZO in a previously healthy, immunocompetent individual. [ABSTRACT FROM AUTHOR]

The integrity of performance appraisal systems depends on the appraiser, responsible for providing employees with objective evaluations. Research has shown that managers often feel anxiety when conducting employee appraisals and consequently may withhold negative feedback, compromising the appraisal process. We examined, using Grounded theory, the manager's experience of performance appraisal anxiety with 13 experienced managers. We found that a primary cause of PA anxiety was the fear that the employee would react negatively to the feedback. Further, our participants described productive levers they use to reduce PA anxiety while preserving the integrity of the feedback provided. PA anxiety was reduced by implementing more frequent feedback, training to increase manager confidence in delivering feedback effectively, and adoption of an employee-centered approach to PA. [ABSTRACT FROM AUTHOR]

The additional prognostic value of resting electrocardiogram (ECG) in long-term cardiovascular disease (CVD)-risk-assessment is unclear. We evaluated the association of incidental abnormal ECG findings with long-term CVD-risk and all-cause mortality, and assessed the additional prognostic value of ECG as a screening tool in adults without known CVD. A cohort of 2601 Israeli men and women without known CVD were actively followed from 1976 to 1982 for 23-year cumulative CVD-incidence, and until May 2017 for all-cause mortality. At baseline and follow-up, participants underwent interviews, physical examinations, blood tests and ECG. At baseline, 1199 (46.1%) had incidental abnormal ECG findings (exposed-group). CVD cumulative incidence reached 31.6% among the 930 survivors who participated in the active follow-up (294/930). During a 31-year median follow-up, 1719 (66.1%) of the total cohort died. Incidental abnormal ECG findings were associated with 46% greater CVD-risk (odds ratio = 1.46, 95%CI = 1.09–1.97). The net reclassification improvement (NRI) of CVD-risk was 7.4% (95%CI NRI = 1.5%–13.3%, p = 0.01) following the addition of ECG findings, but the C-index improvement was not statistically significant [C-index = 0.656 (0.619–0.694) vs. C-index = 0.666 (0.629–0.703), p = 0.14]. Multivariable Cox regression demonstrated an all-cause mortality hazard ratio (HR) of 1.18 (95%CI = 1.07–1.30) for exposed vs. unexposed individuals. Non-specific T-wave changes and left-axis deviation are the incidental ECG abnormalities that were associated with all-cause mortality [HR = 1.18 (95%CI = 1.05–1.33) and HR = 1.19 (95%CI = 1.00–1.42), respectively]. Incidental abnormal ECG findings, mainly non-specific T-wave changes and left-axis deviation, were associated with increased long-term CVD-risk and all-cause mortality among individuals without known CVD, and demonstrated net reclassification improvement for CVD-risk. • Incidental abnormal ECG findings were associated with mortality and CVD risk. • The abnormal ECG findings improved 23-year CVD risk classification of 7.4% adults. • Non-specific T-wave changes and left-axis deviation associated with increased mortality risk. • Screening ECG in low risk healthy adults may improve CVD risk stratification. [ABSTRACT FROM AUTHOR]

To explore how to better educate rural Africans about preventive HIV/AIDS vaccine trials, 15 semi-structured, open-ended interviews were conducted with villagers in Lyantonde, Rakai District, Uganda. This study reports on the findings by focusing on the attitudes, knowledge and questions the rural villagers had about HIV/AIDS-preventive vaccine testing. While several interviewees confused preventive vaccines with therapeutic vaccines, most were clear about the distinction and about key questions to ask about vaccine testing. In addition, some subjects manifested high levels of trust in the likely effectiveness of preventive vaccines, even in the testing stages, most subjects demonstrated the potential to be intelligently inquisitive about the likely effects. In sum, these villagers show the potential to be reliable subjects, motivated for appropriate reasons, and willing to play a role in advancing the progress of HIV/AIDS vaccine development in Africa. [ABSTRACT FROM AUTHOR]

Preventive vaccines are widely acknowledged as the best hope for protection against infectious pathogens such as avian flu, HIV and SARS. As a result, they have received much recent attention in the media that has exposed some of the challenges involved in optimally using vaccine technology. [ABSTRACT FROM AUTHOR]